Posters

New Approach for Qualifying Liquid Handling in Single-Use Bags

2D Flexsafe® Bags and Shells Offer Strong Validation: Complete logistical solution for handling and shipping of liquid bulk drug substance in a 2D Flexsafe® bag & shell Quality by design principles Comprehensive and innovative testing program following the guidelines like ASTM, NF and ISO The system allows for safe variable shipping volumes of 10–120% of nominal fill volume and can be leveraged by the end-users for their own process validation Fill out the form below to view the complete poster…

Antibody Affinity Extraction Enables Identification of Host Cell Proteins by Mass Spectrometry

Host cell proteins (HCP) constitute a major group of impurities for biologic drugs produced using cell culture technology. Even at nanogram per milligram concentrations of HCP to drug substance (DS), HCPs can elicit undesired immune response, interfere with drug safety and efficacy, or impact DS stability. A broadly-reactive HCP ELISA should be used during the purification processes to ensure removal of HCPs and to demonstrate process consistency and final DS purity. Regulatory authorities are requesting biopharmaceutical companies employ orthogonal methods…

Step-wise strategy to address process characterization and late phase development – toward the definition of a standardized approach

Drivers for process characterization and late phase development include improving process understanding, enhancing process robustness, and assurance that the process delivers consistent product quality within all Proven Acceptable Ranges (PARs). Regulator’s expectations for biologic submissions include the application of statistical methods to improve the confidence of the PARs and knowledge of the design space for a process. Different approaches have been reported for process characterization but contain common elements including risk assessment, scale-down model qualification, and statistical design of experiments.…

Characterization and Lot Release Assays for Antibody Drug Conjugates

Antibody-drug conjugates (ADCs) add an additional level of challenge to testing of biotherapeutics. Besides the antibody, which needs to be evaluated for potential and known mechanisms of action (MoA), there is a cytostatic compound conjugated that alters the behavior of the antibody-vehicle within the typical assays. Therefore, characterization of new innovators as well as biosimilarity assessment is even more challenging than it is for antibody therapeutics. Using the example of Trastuzumab emtansine, Charles River has set up a panel of…

Keeping Host Cell Protein ELISAs Covered

Biological drugs (or biologics) are manufactured by living systems such as microorganisms, and plant and animal cells. Cell lines, like Chinese hamster ovary (CHO), can be engineered to work as cellular factories to produce biologics in addition to their own biological molecules. Host cell proteins (HCPs) are biological by-products of these cellular factories. They are one of the main impurities in harvested cell culture fluid (HCCF), and tend to be released when the cells die or are damaged. These HCPs…

Removal of Isoagglutinins from IVIG and Plasma Using Affinity Chromatography

Antibody-mediated haemolysis is a hard-to-predict phenomenon with potentially severe consequences. It is mediated by naturally-occurring anti-A and anti-B immunoglobulin isoagglutinins, which are present in plasma, blood, and several derived products, including IVIG produced by plasma fractionation. Prometic Bioseparations have developed an affinity chromatography resin for the removal of isoagglutinins from plasma and plasma derived products, such as IVIG. The resins, IsoClear A and IsoClear B, can clear isoagglutinins from a titre of 1/32 down to negative agglutination using a load…

Expansion, Recovery and Characterization of hMSCs on Dissolvable Microcarriers for Bioprocess Applications

Human mesenchymal stem cells (hMSCs) are currently the most common adult stem cell type used for cell therapy applications due to their regenerative properties and ability to differentiate into multiple cell lineages (adipocyte, chondro¬cyte, and osteocyte). Traditionally, hMSCs have been cultured on two-dimensional cell culture platforms using serum-containing medium. Although these platforms can be used successfully for small-scale expansion of hMSCs, other platforms will be required to generate the quantity of cells required to support the increasing number of clinical…

Development of a Next Generation Cellulose-Based High Capacity rProtein A Capture Resin for High Throughput MAb Purification in Both Batch and Continuous Purification Formats

A new product development approach will be described for the affinity capture of Mab’s from cell culture materials employing a novel base stable rProtein A ligand. Using a stable cellulose base bead with excellent flow properties coupled with a novel immobilization methodology, a next generation rProtein A capture resin has been developed with a high level of antibody binding capacity. The new Cellufine™ rProtein A resin shows C20% dynamic binding capacity (DBC) of >50 mg/ mL with polyclonal antibodies at…

Long-Term Reliability of an Aseptic On-line Glucose Monitoring and Control System for Perfusion CHO Cell Culture

Among the variables that are appropriate for direct feedback control of the perfusion rate in mammalian cell cultures, high priority should be given to the glucose concentration. Here we describe the application of a closed-loop control scheme for the long-term cultivation of CHO cells in a high cell density (35 – 40 million cells/ml) perfusion process. The monitoring and control system worked successfully for 2.5 months without any signs of performance degradation. In targeting industrial applications, issues such as reliability,…

Beta Cyclodextrin Derivatives as Protein Aggregation Modulators

Protein aggregation is the major challenge encountered during manufacturing, storage and transportation of biopharmaceuticals (1,2). The objective was to evaluate the effect of two ßcyclodextrins derivatives: (KLEPTOSE® HPB hydroxypropyl-ß-cyclodextrin, with MS=0.65) and (KLEPTOSE® HP hydroxypropyl-ß-cyclodextrin, with MS=0.9) on two biologic drugs (Infliximab and Etanercept) aggregation using high-throughput formulation screening (iFormulate™) and nanoDSF (Differential Scanning Fluorimetry) (3,4). Preliminary results demonstrate that KLEPTOSE® HPB BioPharma hydroxypropyl-ß-cyclodextrin and KLEPTOSE® HP BioPharma hydroxypropyl-ß-cyclodextrin at high molarity (200 mM) are efficient tools in modulating Infliximab…